2 Структура и функция белка (1160071), страница 28
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Their catalytic activity depends uponthe integrity of their native protein conformation. If an enzyme is denatured or dissociated into subunits, catalytic activity is usually lost. Ifan enzyme is broken down into its component amino acids, its catalyticactivity is always destroyed. Thus the primary, secondary, tertiary,and quaternary structures of protein enzymes are essential to theircatalytic activity.Enzymes, like other proteins, have molecular weights rangingfrom about 12,000 to over 1 million.
Some enzymes require no chemicalgroups other than their amino acid residues for activity. Others require an additional chemical component called a cofactor. The cofactor may be either one or more inorganic ions, such as Fe 2 + , Mg 2+ ,Mn 2+ , or Zn 2+ (Table 8-1), or a complex organic or metalloorganic molecule called a coenzyme (Table 8-2). Some enzymes require both acoenzyme and one or more metal ions for activity. A coenzyme or metalion that is covalently bound to the enzyme protein is called a prosthetic group. A complete, catalytically active enzyme together withits coenzyme and/or metal ions is called a holoenzyme.
The proteinpart of such an enzyme is called the apoenzyme or apoprotein. Coenzymes function as transient carriers of specific functional groups(Table 8-2). Many vitamins, organic nutrients required in smallamounts in the diet, are precursors of coenzymes. Coenzymes will beconsidered in more detail as they are encountered in the discussion ofmetabolic pathways in Part III of this book.Figure 8-1 Crystals of pyruvate kinase, an enzyme of the glycolytic pathway. The protein in acrystal is generally characterized by a high degreeof purity and structural homogeneity.200Part II Structure and CatalysisTable 8-1 Some enzymes containing orrequiring inorganic elements as cofactorsF e 2 + or F e 3 +Cu2+Zn2+Cytochrome oxidaseCatalasePeroxidaseCytochrome oxidaseNi2+Carbonic anhydraseAlcohol dehydrogenaseHexokinaseGlucose-6-phosphatasePyruvate kinaseArginaseRibonucleotide reductasePyruvate kinaseUreaseMoSeDinitrogenaseGlutathione peroxidaseMg2+Mn2+K+Table 8—2 Some coenzymes serving as transient carriers of specificatoms or functional groups4"CoenzymeThiamine pyrophosphateFlavin adeninedinucleotideNicotinamide adeninedinucleotideCoenzyme AExamples of somechemical groupstransferredDietary precursorin mammalsAldehydesElectronsThiamin (vitamin B^Riboflavin (vitamin B2)Hydride ion (:H~)Nicotinic acid (niacin)Acyl groupsPantothenic acid, plusother moleculesPyridoxine (vitamin B6)Vitamin B12Pyridoxal phosphate5' -Deoxyadenosylcobalamin(coenzyme B12)BiocytinAmino groupsH atoms and alkylgroupsco2BiotinTetrahydrofolateLipoateOne-carbon groupsElectrons and acylgroupsFolateNot requiredin diet* The structure and mode of action of these coenzymes are described in Part III of this book.Finally, some enzymes are modified by phosphorylation, glycosylation, and other processes.
Many of these alterations are involved in theregulation of enzyme activity.Enzymes Are Classified by the Reactions They CatalyzeMany enzymes have been named by adding the suffix "-ase" to thename of their substrate or to a word or phrase describing their activity.Thus urease catalyzes hydrolysis of urea, and DNA polymerase catalyzes the synthesis of DNA. Other enzymes, such as pepsin and trypsin, have names that do not denote their substrates. Sometimes thesame enzyme has two or more names, or two different enzymes havethe same name. Because of such ambiguities, and the ever-increasingnumber of newly discovered enzymes, a system for naming and classifying enzymes has been adopted by international agreement.
This system places all enzymes in six major classes, each with subclasses,based on the type of reaction catalyzed (Table 8-3). Each enzyme isassigned a four-digit classification number and a systematic name,which identifies the reaction catalyzed. As an example, the formal systematic name of the enzyme catalyzing the reactionATP + D-glucoseADP + D-glucose-6-phosphateis ATP:glucose phosphotransferase, which indicates that it catalyzesthe transfer of a phosphate group from ATP to glucose. Its enzymeclassification number (E.C.
number) is 2.7.1.1; the first digit (2) denotesthe class name (transferase) (see Table 8-3); the second digit (7), theChapter 8 Enzymes201Table 8-3 International classification of enzymes*No.ClassType of reaction catalyzed1Oxidoreductases23TransferasesHydrolases4Lyases5Isomerases6LigasesTransfer of electrons(hydride ions or H atoms)Group-transfer reactionsHydrolysis reactions (transfer of functionalgroups to water)Addition of groups to double bonds, or formationof double bonds by removal of groupsTransfer of groups within molecules to yieldisomeric formsFormation of C—C, C—S, C—O, and C—N bondsby condensation reactions coupled to ATPcleavage* Most enzymes catalyze the transfer of electrons, atoms, or functional groups. They are thereforeclassified, given code numbers, and assigned names according to the type of transfer reaction,the group donor, and the group acceptor.subclass (phosphotransferase); the third digit (1), phosphotransferaseswith a hydroxyl group as acceptor; and the fourth digit (1), D-glucose asthe phosphate-group acceptor.
When the systematic name of an enzyme is long or cumbersome, a trivial name may be used—in this casehexokinase.A complete list and description of the thousands of known enzymeswould be well beyond the scope of this book. This chapter is insteaddevoted primarily to principles and properties common to all enzymes.How Enzymes WorkThe enzymatic catalysis of reactions is essential to living systems.Under biologically relevant conditions, uncatalyzed reactions tend tobe slow. Most biological molecules are quite stable in the neutral-pH,mild-temperature, aqueous environment found inside cells.
Many common reactions in biochemistry involve chemical events that are unfavorable or unlikely in the cellular environment, such as the transientformation of unstable charged intermediates or the collision of two ormore molecules in the precise orientation required for reaction. Reactions required to digest food, send nerve signals, or contract musclesimply do not occur at a useful rate without catalysis.An enzyme circumvents these problems by providing a specificenvironment within which a given reaction is energetically more favorable.
The distinguishing feature of an enzyme-catalyzed reaction isthat it occurs within the confines of a pocket on the enzyme called theactive site (Fig. 8-2). The molecule that is bound by the active siteand acted upon by the enzyme is called the substrate. The enzymesubstrate complex is central to the action of enzymes, and it is thestarting point for mathematical treatments defining the kinetic behavior of enzyme-catalyzed reactions and for theoretical descriptions ofenzyme mechanisms.Figure 8—2 Binding of a substrate to an enzymeat the active site. The enzyme chymotrypsin isshown, bound to a substrate (in blue). Some keyactive-site amino acids are shown in red.202Part II Structure and CatalysisEnzymes Affect Reaction Rates, Not EquilibriaA tour through an enzyme-catalyzed reaction serves to introduce someimportant concepts and definitions.A simple enzymatic reaction might be writtenE +STransition state ($)Reaction coordinateFigure 8-3 Reaction coordinate diagram for achemical reaction.
The free energy of the system isplotted against the progress of the reaction. A diagram of this kind is a description of the energeticcourse of the reaction, and the horizontal axis (reaction coordinate) reflects the progressive chemicalchanges (e.g., bond breakage or formation) as S isconverted to P. The S and P symbols mark the freeenergies of the substrate and product groundstates. The transition state is indicated by the symbol $. The activation energies, AG*, for the S —> Pand P —> S reactions are indicated. AG°' is the overall standard free-energy change in going from Sto P.E +P(8-1)where E, S, and P represent the enzyme, substrate, and product, respectively.
ES and EP are complexes of the enzyme with the substrateand with the product, respectively.To understand catalysis, we must first appreciate the importantdistinction between reaction equilibria (discussed in Chapter 4) andreaction rates. The function of a catalyst is to increase the rate of areaction. Catalysts do not affect reaction equilibria. Any reaction, suchas S ^ P, can be described by a reaction coordinate diagram (Fig. 8-3).This is a picture of the energetic course of the reaction.
As introducedin Chapters 1 and 3, energy in biological systems is described in termsof free energy, G. In the coordinate diagram, the free energy of thesystem is plotted against the progress of the reaction (reaction coordinate). In its normal stable form or ground state, any molecule (suchas S or P) contains a characteristic amount of free energy. To describethe free-energy changes for reactions, chemists define a standard set ofconditions (temperature 298 K; partial pressure of gases each 1 atm or101.3 kPa; concentration of solutes each 1 M), and express the freeenergy change for this reacting system as AG°, the standard freeenergy change. Because biochemical systems commonly involve H+concentrations far from 1M, biochemists define a constant AG0', thestandard free-energy change at pH 7.0, which we will employ throughout the book.
A more complete definition of AG°' is given in Chapter 13.The equilibrium between S and P reflects the difference in the freeenergy of their ground states. In the example shown in Figure 8-3, thefree energy of the ground state of P is lower than that of S, so AG°' forthe reaction is negative and the equilibrium favors P. This equilibriumis not affected by any catalyst.A favorable equilibrium, however, does not mean that the S —> Pconversion is fast. The rate of a reaction is dependent on an entirelydifferent parameter. There is an energetic barrier between S and Pthat represents the energy required for alignment of reacting groups,formation of transient unstable charges, bond rearrangements, andother transformations required for the reaction to occur in either direction.
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